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The increasing use of aluminum nanoparticles (nano-Al) leads to increased human exposure and might affect human health. Considering the suggested connection between aluminum exposure and Alzheimer's disease (AD) pathogenesis, there is a concern about the effect of nano-Al on cognitive function and brain health. This study was aimed to assess the effect of a 5-day oral gavage of aluminum oxide nanoparticle (nano-Al) on memory and the phosphorylation levels of hippocampal p38, JNK (c-Jun N-terminal kinase), ERK (extracellular signal-regulated kinase) as well as cleaved caspase-3 in mice. Adult male NMRI mice were treated with nano-Al in doses 5 and 10 mg/kg/oral gavage for 5 days. The test session of novel object recognition (NOR) task was performed on day 5. Following the NOR test, the hippocampi were isolated for western blot analysis to determine the total and phosphorylated levels of p38, JNK, ERK as well as cleaved caspase-3 proteins. The results showed that nano-Al oral gavage in doses of 5 and 10 mg/kg impairs NOR memory in mice. Moreover, the memory impairing effect of nano-Al coincided with a dose dependent increase in phosphorylated p38 and cleaved caspase-3 in the hippocampus. It also increased the ratio of phosphorylated to total content of ERK in the hippocampus while JNK signaling was not affected by nano-Al. This study showed that nano-Al in doses as low as 5 and 10 mg/ kg ingested for 5 days impairs NOR memory and activates p38, ERK and cleaved caspase-3 in the hippocampus., (Copyright © 2021 Elsevier B.V. All rights reserved.)